Emerging and re-emerging viral diseases, predisposing risk factors, and implications of international travel: a call for action for increasing vigilance and imposing restrictions under the current threats of recently emerging multiple Omicron subvariants
Authors: Oroshay Kaiwan, Yashendra Sethi, Nimrat Khehra, Inderbir Padda, Hitesh Chopra, Deepak Chandran, Kuldeep Dhama, Chiranjib Chakraborty, Md. Aminul Islam, Nirja Kaka
Journal: International Journal of Surgery (2023)

Viruses, especially single-stranded RNA viruses, have always been a pathogenic menace as they cause emerging infectious diseases such as Zika, Ebola, Bird Flu, Chikungunya, Dengue, MERS, Coronavirus Disease 2019 (COVID-19), Mokeypox, Marburg, Polio, and others. Of note, severe acute respiratory syndrome coronavirus 2 Delta and Omicron variants have posed significant global health impacts during the COVID-19 pandemic, co-circulation, and co-infections caused emergence of recombinant and hybrid variants, and eventually leading to different waves of surge in cases due to evasion of the vaccine (vaccine breakthrough) and infection induced immunity1. Currently, Omicron subvariants and lineages such as BA.1, BA.2, BA.3, BA.4, BA.5, and then BQ.1, BQ.1.1, BA.4.6, BF.7, BA.2.75.2, XBB.1 and BF.7 have created additional health burden, revealing escape from vaccine and viral infection induced protective immunity1–4. A significant surge in COVID-19 cases has been seen from time to time in 2022, and more recently, cases of COVID-19 are again being observed to be rising in a few countries, especially China, evidencing an unprecedented high rise owing to the Omicron BF.7 subvariant and thus posing fears of the feasibility of driving a new wave of pandemic ahead4,5. Therefore, while transmissibility and disease severity of most recently emerged Omicron subvariants are still being investigated, it is strongly encouraged to resume appropriate COVID-19 behavior protocols, adopt recommended prevention and control measures, especially airborne and contact precautions for avoiding infection, and also consider the significance of increasing vigilance and imposing restrictions on international travel, may be partial as deemed fit from time to time, unless and until the ongoing COVID-19 pandemic comes to an end. Many factors contribute to the emergence of viruses. Human factors include urbanization, globalization, immune status, demographics, and international travel. Environmental factors include weather and climate changes (El Niño effects), river damming (which affects the amount and distribution of possible viral vectors or hosts), tropical deforestation (forcing human-vector contact), ecological interactions, pollution, and disturbances to the equilibrium. Viral factors include the genetic makeup of the virus, viral genetic variations (mutation, reassortment, and recombination), and specific changes (antigenic shift and drift in the influenza virus). It is imperative to mention, that emerging viral diseases are zoonoses, which are predominantly spread by arthropods and nonhuman primates6. The emergence can be explained by the phenomenon of 'Microbial traffic' which refers to the mechanism through which infectious organisms can spread from animals to people or from isolated groups into new populations. A variety of activities boost microbial movement, promoting emergence and epidemics. In certain cases, the agents spread from their native habitat into the human population due to the many similarities. In other circumstances, infections that are already present in geographically isolated groups are given a chance to spread further. Unexpectedly, human actions often lead to the genesis of these outbreaks; occasionally, natural factors like climatic shifts can also play a role. The spread of new and re-emerging infectious illnesses throughout the world is facilitated in large part by international travel, the most recent great example being the COVID-19 pandemic7–9. The importation of infectious diseases has long been a concern that is disregarded in countries with developing economies, despite the fact that it poses a serious health issue Increases in the incidence of imported infectious diseases may be linked to the boom in worldwide travel and globalization. However, monitoring programs have not reflected the rise in imported infectious disease incidences because they do not adequately capture complete epidemiological data10,11. Most new infectious disease outbreaks start in animals, and this trend is growing as a result of human activity, including increased mobility and globalization, and shifting environmental conditions, such as climate change and global warming. The most vulnerable populations, vectors of transmission, fatality rate, and transmissibility (typically expressed as a basic reproduction number) vary greatly between different viral disease epidemics12. Despite these variations, policy responses to viral epidemics tend to be consistent over time and across countries. These responses include social isolation, quarantine, school closures, and information campaigns, as well as vector control campaigns for vector-borne viral diseases, personal protection, and vaccines. Strict mobility and travel limitations are being implemented for illnesses with a high potential for geographic spread coupled with significant case mortality13,14, and full high limitations as like during COVID-19 pandemic7,8. As the world becomes more interconnected and mobile, international travel and trade have become increasingly important in shaping the spread and resurgence of infectious illnesses. There are three ways in which travel is linked to the spread of disease: the disease first appears in an area that sees a lot of visitors; the behaviors of the tourists themselves may put them in danger; or the travelers themselves act as vectors to spread the agent to other places15,16. In the age of globalization, international travel has improved connectivity but it has also allowed the transmission of seeds of outbreak from one region to another7,8. This is further augmented by ecological factors, which typically precipitate emergence by bringing individuals into direct contact with a previously unknown but pre-existing natural reservoir or host for an infection (often a zoonotic or arthropod-borne infection), either by increasing proximity or, more frequently, by changing situations to support an increasing growth of the microbe or its natural host17. The recent COVID-19 pandemic and its long-lasting impacts have made us realize the importance of preventive measures and pandemic preparedness as well as emphasizing the importance of restrictions on international travel either partial or full bans on flights, and adopting adequate mitigation measures during travel7–9. International travel is increasingly becoming more regulated. However, political, economical, and emotional factors hinder timely action. It has been laid out in a catena of research that travel restrictions must be implemented quickly to postpone the peak of a future outbreak7. A stronger and more portable diagnostic framework can prevent emerging viral infections from becoming pandemics or epidemics by aiding in early diagnosis and treatment. Diagnostic criteria can include point-of-care (POC) testing and the incorporation of artificial intelligence (AI) into healthcare systems. However, the gold standard for diagnostic methods remains reverse transcription-PCR (RT-PCR) for many emerging infections. POC molecular diagnostics significantly aid testing expansion, offer a portable, cost-effective solution, and eliminate the over-reliance on centralized laboratories18. POC can also measure different entities (viruses, antigens, and antibodies) that can contribute to the precise determination of an individual's health status. Early and accurate testing can decide a patient's clinical course and aid in management. However, a major challenge to this approach is the development and scaling of reliable methods for emerging infections for molecular detection and serologic assays in a timely fashion. AI can be used during outbreaks of emerging viral infections by detecting the transmission or predicting high-risk patients to help develop appropriate infection prevention and control (IPC) measures. AI can improve diagnostics by providing objective pattern recognition, standardizing the diagnosis of infections with IPC implications, and disseminating expertise in IPC19. The essence of the prevention of emerging viral infections is vaccines, and advances in science and technology have paved the ways for designing and developing effective, improved, and modern vaccines, including recombinant vaccines, vector-based vaccines, DNA vaccines, plant-based vaccines, CRISPR- and artificial intelligence-based vaccines, and others. We have seen repurposed vaccines having great success against certain emerging viruses, but had we been better prepared, we could have saved more people from mortality and morbidity caused by COVID-19. Furthermore, we need to refine the prophylactic and empirical treatment options. Most direct-acting antivirals take a 'one drug, one bug' approach by inhibiting proteins encoded by a single virus and end up being expensive yet inefficient against emerging infections. A possible cost-efficient solution in this domain is to target the host cell machinery or enzymatic functions shared by multiple viruses (broad-spectrum antivirals)20. Different interventions fall under the umbrella of 'travel-related control measures', including the complete closure of national borders to entry or exit, or both; travel restrictions reducing or stopping cross-border travel (e.g. denial of entry or exit based on nationality, travel history, health status, or other characteristics; suspension of travel via air, land, and sea); symptom/exposure-based screening at borders; test-based screening at borders; quarantine of travelers; wearing of face masks, and so on9,21,22. Taking precautions against the spread of infectious diseases through travel is a well-established method in public health. The widespread use of quarantine in medieval port towns and other areas helped stop the spread of bubonic plague. Recent epidemics have seen the implementation of similar procedures, such as airport exit screening and entry screening at national borders during the severe acute respiratory syndrome coronavirus 2 outbreak in 2019–2022, and airport exit screening during the Ebola outbreak in West Africa and the Democratic Republic of the Congo in 2014–201622. Considering that international travel plays a major role in the spread of emerging infectious pathogens, the authorities have imposed respiratory and hand hygiene for all travelers, but these interventions are not enough at a public health level. The travel regulations and restrictions form an immediate administrative need and have seen significant developments after COVID-19, laying the groundwork to manage future outbreaks too. Major citable examples are the 'travel bubbles' and 'vaccine passports'. A travel bubble is an arrangement, where bilateral air travel between two economically dependent countries is carried out given the testing protocols are maintained8. Another legislative tool is the 'vaccine passport'. These documents or certificates allow the authorities to ensure that all travelers are vaccinated23. In general, the timely imposition of appropriate restrictions on international travel could help prevent the spread of infectious diseases from one country to another. If the quarantine time is long enough and compliance is high, it should be possible to prevent the spread of the disease through tourists. Combining quarantine with PCR and POC diagnostic testing at borders is anticipated to increase efficiency. Studies have shown that the effectiveness of public health measures can vary widely depending on a variety of variables, including the prevalence of the disease in the community, the number of people who travel, the distance they travel, the types of public health measures already in place, and when they are implemented21,22. Better reporting, a variety of research approaches beyond modeling, and a societal assessment of the possible benefits and hazards of travel-related control measures are all necessary for future research. To save the world from the impacts of recently emerging multiple Omicron subvariants posing the feasibility of a new wave of COVID-19 pandemics, and other future pandemics, we recommend well-planned country-specific legislative policies for imposing time-to-time restrictions on international travel, enhancing more collaborative research for developing broad-spectrum antivirals and effective and newer vaccines, and strengthening preplanned structures for vaccine repurposing. Mitigation of the spread of Omicron subvariants warrants an integrated and collaborative IPC approach that combines masking, physical distancing, improving ventilation, increased testing, vigilance, tracking, isolation, quarantine, and awareness to counteract the COVID-19 pandemic in an effective way. Ethical approval The authors declare no involvement of animal studies or human participants in the study as it is a compiled letter article. Sources of funding None. Author contribution O.K., Y.S., N.K., and I.P.: designed the study. Y.S., H.C., and D.C.: made the first draft. Y.S., K.D., C.C., A.I., and N.K.: updated the manuscript. Y.S. and K.D.: reviewed the final draft. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript. Conflicts of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) None. Guarantor Md. Aminul Islam, COVID-19 Diagnostic Lab, Department of Microbiology, Noakhali Science and Technology University, Noakhali 3814, Bangladesh. Data statement Data not available/not applicable.